High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation

• Published in: Circulation (New York, N.Y.) Vol. 85; no. 3; pp. 1077 - 1082
• Main Authors: RATNATUNGA, C. P, EDMONDSON, S. F, REES, G. M, KOVACS, I. B
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-03-1992
• Subjects: Aspirin - administration & dosage; Aspirin - therapeutic use; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Coronary Artery Bypass; Dose-Response Relationship, Drug; Female; Hemostasis - drug effects; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Platelet Aggregation - physiology; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - therapeutic use; Postoperative Complications - prevention & control; Thrombin - biosynthesis; Thrombosis - prevention & control; Thromboxanes - biosynthesis; Human; Coronary artery; Cardiovascular disease; Exploration; Coronary heart disease; Thrombosis; Antiplatelet agent; Prevention; Chemotherapy; Platelet; Treatment; Aortocoronary; Bypass; Surgery; High dose
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.85.3.1077

A unifying concept of explaining all pharmacological actions of aspirin by the irreversible blockage of the enzyme cyclooxygenase and therefore the inhibition of prostaglandin biosynthesis has left many unanswered questions.
Two hundred ninety-four patients taking 75 mg/day aspirin were tested 3 months after coronary artery bypass surgery. Platelet thromboxane formation (whole blood aggregation to arachidonate) was completely prevented in 80% of patients. Compared with matched healthy controls (n = 95), a significant platelet hyperreactivity was observed in patients (p less than 0.0001 versus less than 0.002). Ninety patients were advised to increase their daily dose of aspirin from 75 mg to 300 mg. Platelet reactivity retested 1 month after increasing the dose has significantly decreased (p = 0.0008; less than 0.0001), whereas it remained unchanged in those patients (n = 84) who continued with the same dose regimens. In normal subjects, ingestion of a single 600-mg aspirin significantly inhibited shear-induced platelet reaction.
It is concluded that aspirin does affect the platelet response to shear forces, but this requires higher dosage (greater than 300 mg/day), suggesting a mechanism probably different from that of interference with thromboxane formation.